Electrical stimulation of the superior sagittal sinus suppresses A-type K+ currents and increases P/Q- and T-type Ca2+ currents in rat trigeminal ganglion neurons

Abstract

BackgroundMigraine is a debilitating neurological disorder involving abnormal trigeminovascular activation and sensitization. However, the underlying cellular and molecular mechanisms remain unclear.MethodsA rat model of conscious migraine was established through the electrical stimulation (ES) of the dural mater surrounding the superior sagittal sinus. Using patch clamp recording, immunofluorescent labelling, enzyme-linked immunosorbent assays and western blot analysis, we studied the effects of ES on sensory neuronal excitability and elucidated the underlying mechanisms mediated by voltage-gated ion channels.ResultsThe calcitonin gene-related peptide (CGRP) level in the jugular vein blood and the number of CGRP-positive neurons in the trigeminal ganglia (TGs) were significantly increased in rats with ES-induced migraine. The application of ES increased actional potential firing in both small-sized IB4-negative (IB4−) and IB4+ TG neurons. No significant changes in voltage-gated Na+ currents were observed in the ES-treated groups. ES robustly suppressed the transient outward K+ current (IA) in both types of TG neurons, while the delayed rectifier K+ current remained unchanged. Immunoblot analysis revealed that the protein expression of Kv4.3 was significantly decreased in the ES-treated groups, while Kv1.4 remained unaffected. Interestingly, ES increased the P/Q-type and T-type Ca2+ currents in small-sized IB4− TG neurons, while there were no significant changes in the IB4+ subpopulation of neurons.ConclusionThese results suggest that ES decreases the IA in small-sized TG neurons and increases P/Q- and T-type Ca2+ currents in the IB4− subpopulation of TG neurons, which might contribute to neuronal hyperexcitability in a rat model of ES-induced migraine.

P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine

“…Our results indicated that the reduced periorbital mechanical pain threshold and increased spontaneous pain behavior of the IS mice can be alleviated by inhibition of P2X7R (Fig. 9 ), supporting the previous findings [ 52 , 53 ]. The results of cognitive behavior tests showed that the IS mice exhibited a poor recognition memory in novel object recognition test, and impaired spatial memory retention in probe trial of Morris water maze, but no obvious impairment of spatial learning ability in the learning period of Morris water maze (Fig.…”

Cortical pain induced by optogenetic cortical spreading depression: from whole brain activity mapping

“…Electrical stimulation (ES) of dural mater surrounding superior sagittal sinus could well mimic the process and behavior of migraine. Previous studies have found that ES could suppress the outward K + current and increase the excitability of neurons in TG, which induces headache [ 47 ]. Therefore the ES model is a relatively ideal model for migraine without aura.…”

Interleukin 33-mediated inhibition of A-type K+ channels induces sensory neuronal hyperexcitability and nociceptive behaviors in mice

“…Total RNA was extracted from mouse lumbar (L4-6) DRGs using an RNeasy Plus Mini kit (Qiagen) as described previously 32 , 33 . RNA was reverse-transcribed using SuperScript TM III reverse transcriptase (Thermo Scientific).…”

“…Immunoblot analysis was performed as described in our previous studies 27 , 32 , 34 . In brief, samples containing 25 μg of protein were separated on SDS-polyacrylamide gel electrophoresis, electroblotted onto polyvinylidene difluoride membranes (Merk Millipore), and probed with antibodies against ST2/IL-33R (rabbit, 1:1000; Novus Biologicals, Cat.…”